Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Am J Physiol Gastrointest Liver Physiol. 2011 Mar;300(3):G401-8. doi: 10.1152/ajpgi.00351.2010. Epub 2010 Dec 16.
The pathogenesis of ulcerative colitis (UC) is unclear, but enhancement of disease activity by usage of nonsteroidal anti-inflammatory drugs suggests involvement of prostanoid in its pathophysiology. However, biological effect of prostaglandin (PG) D(2) on intestinal inflammation remains unknown. We investigated the expression of enzymes for PGD(2) synthesis, prostaglandin D synthase (PGDS), and its relation to the activity of colitis in UC patients. The role of lipocalin-type PGDS (L-PGDS) using a murine colitis model was also assessed. Tissue samples were obtained by colonic biopsies from patients with UC. Expression levels of mRNAs for L-PGDS and hematopoietic-type PGDS were investigated by quantitative RT-PCR. COX-2 and L-PGDS expression was investigated by immunohistochemistry. Localization of L-PGDS expression was also determined by in situ hybridization. In experimental study, mice were treated with dextran sodium sulfate in the drinking water to induce colitis. The degree of colonic inflammation was compared with L-PGDS(-/-) mice and control mice. The level of L-PGDS mRNA expression was increased in UC patients in parallel with disease activity. Colocalization of L-PGDS and cyclooxygenase (COX) 2 was observed in lamina proprial infiltrating cells and muscularis mucosa in UC patients. The level of hematopoietic PGDS mRNA expression did not differ from control mucosa. Dextran sodium sulfate treatment to L-PGDS(-/-) mice showed lower disease activity than control mice. We reported for the first time the presence of L-PGDS in the COX-2-expressing cells in the mucosa of active UC patients and that only L-PGDS increased with disease activity. An animal model study suggests that PGD(2) derived from L-PGDS-expressing cells plays proinflammatory roles in colitis.
溃疡性结肠炎（UC）的发病机制尚不清楚，但非甾体抗炎药的使用增强了疾病的活动度，提示前列腺素（PG）在其病理生理学中发挥作用。然而，前列腺素 D2（PGD2）对肠道炎症的生物学效应尚不清楚。我们研究了 PGDS 及其与 UC 患者结肠炎活动度的关系。还评估了脂钙蛋白型 PGDS（L-PGDS）在鼠结肠炎模型中的作用。通过结肠活检获得 UC 患者的组织样本。通过定量 RT-PCR 研究 L-PGDS 和造血型 PGDS 的 mRNA 表达水平。通过免疫组化研究 COX-2 和 L-PGDS 的表达。通过原位杂交确定 L-PGDS 表达的定位。在实验研究中，用葡聚糖硫酸钠（DSS）处理饮用水诱导结肠炎。将结肠炎症的严重程度与 L-PGDS（-/-）小鼠和对照小鼠进行比较。L-PGDS mRNA 表达水平在 UC 患者中与疾病活动度平行增加。在 UC 患者的固有层浸润细胞和肌层粘膜中观察到 L-PGDS 与环加氧酶（COX）2 的共定位。造血 PGDS mRNA 表达水平与对照粘膜无差异。L-PGDS（-/-）小鼠用 DSS 处理后疾病活动度低于对照小鼠。我们首次报道了在活动期 UC 患者的粘膜中 COX-2 表达细胞中存在 L-PGDS，并且只有 L-PGDS 随着疾病活动度的增加而增加。动物模型研究表明，来源于 L-PGDS 表达细胞的 PGD2 在结肠炎中发挥促炎作用。
